Tyleckova Jirina, Hrabakova Rita, Mairychova Katerina, Halada Petr, Radova Lenka, Dzubak Petr, Hajduch Marian, Gadher Suresh J, Kovarova Hana
Institute of Animal Physiology and Genetics AS CR, v.v.i., 277 21 Libechov, Czech Republic.
Int J Mol Sci. 2012 Nov 22;13(12):15536-64. doi: 10.3390/ijms131215536.
A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%-2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.
通过与相关未处理对照进行配对比较以及对处理和未处理样本进行多变量分类，监测和评估了T淋巴细胞白血病细胞的综合蛋白质组图谱及其在柔红霉素、阿霉素和米托蒽醌处理后的变化。主要关注凋亡影响最小化的早期时间间隔，我们发现蛋白质水平存在显著差异，这些差异蛋白质占检测到的蛋白质斑点总量的1%-2%。根据基因本体生物学过程分类，所有三种药物鉴定出的蛋白质中，最高比例属于蛋白质和核酸的代谢过程以及细胞过程，主要是细胞骨架组织和泛素-蛋白酶体途径。重要的是，我们观察到柔红霉素典型的参与前体代谢物和能量生成的蛋白质、参与阿霉素反应的转运蛋白以及一组表征米托蒽醌反应的免疫系统蛋白质中有显著比例的变化。配对比较和定量数据的多变量评估均显示柔红霉素是蒽环类/蒽二酮类药物中的独特成员。已鉴定的药物特异性蛋白质变化组合可能有助于解释抗癌活性，同时阻断适应性癌症途径激活的益处，为改善癌症治疗结果提供了重要方法。
